Dr. Jennifer S. Temel

Treatment with anamorelin, a highly selective ghrelin receptor agonist, resulted in significant increases in lean body mass and body weight in patients with advanced non–small cell lung cancer (NSCLC) and cachexia compared with placebo, according to the results of the ROMANA 1 and 2 trials presented during the Patient and Survivor Care Oral Abstract Session on Monday, June 1 (Abstract 9500).

“[Although] there are available medications that increase appetite, these medications have some serious side effects,” study presenter Jennifer S. Temel, MD, told ASCO Daily News. “Anamorelin improved symptoms of anorexia/cachexia and impacted cachexia, and so it represents a novel therapeutic option for patients with anorexia/cachexia.”

According to Dr. Temel, patients with cancer and anorexia or cachexia often experience a decreased quality of life, lower chemotherapy tolerance, reduced physical functioning, and worse survival.

The phase III ROMANA 1 (484 patients) and ROMANA 2 (495 patients) trials were 12-week studies that randomly assigned patients with inoperable advanced NSCLC and cachexia 2:1 to 100 mg of anamorelin orally once daily or placebo. Cachexia was defined at 5% or greater weight loss within the prior 6 months or a body mass index of less than 20 kg/m2. The coprimary endpoints of the study were change at 12 weeks in lean body mass and handgrip strength.

Fig. 1.

Fig. 1.

Patients assigned to anamorelin had a significant increase in lean body mass in both ROMANA 1 (1.10 vs. -0.44 kg; p < 0.001) and ROMANA 2 (0.75 vs. -0.96 kg; p < 0.001), but no difference in handgrip strength was found in either of the study arms.

“The increase in lean body mass suggests an increase in muscle mass, which we hoped to see reflected in the handgrip strength, but it is possible that handgrip strength is simply not a good measure for functional changes in muscle or strength,” Dr. Temel said. “Additional recent studies of medications for anorexia/cachexia have also not shown improvements in handgrip strength.”

Overall, treatment with anamorelin was well tolerated, and the rate of grade 3/4 adverse events was low, with no significant difference between the study arms.

A pooled overall survival analysis at 1 year showed no difference in survival between the two study arms.

Commenting on the results of the study, Jamie H. Von Roenn, MD, FASCO, of the American Society of Clinical Oncology, said that anamorelin is “the most effective agent we have yet seen for the treatment of anorexia/cachexia,” but she added that handgrip may not have been the best measure of physical capability, and, overall, may not be an entirely relevant measure in women. Instead, researchers may want to consider a more global evaluation of physical function in the future, such as the use of an accelerometer to monitor physical activity.